Background

There are different way to treat Crohns' disease. We would like to look at the usage pattern for 6 different drugs across four health system.

The data was derived from PEDSNET database V4.1. Orignal datasets were created and processed in SAS.

We are interested in look at different treatment pattrens based on route of administration: IV or oral(subQ) for those exposure drugs. Patients who had at least 2 visits were included in this analysis. First, let's look at IV drugs.

IV drugs

Infliximab

Infliximab cohort summary

Infliximab cohort summary
chop
(N=1168)
colorado
(N=245)
nationwide
(N=394)
nemours
(N=512)
Overall
(N=2319)
Gender
Female 505 (43.2%) 91 (37.1%) 167 (42.4%) 205 (40.0%) 968 (41.7%)
Male 663 (56.8%) 154 (62.9%) 227 (57.6%) 307 (60.0%) 1351 (58.3%)
Race
Black 140 (12.0%) 16 (6.5%) 59 (15.0%) 76 (14.8%) 291 (12.5%)
Other race 151 (12.9%) 49 (20.0%) 32 (8.1%) 65 (12.7%) 297 (12.8%)
White 877 (75.1%) 180 (73.5%) 303 (76.9%) 371 (72.5%) 1731 (74.6%)
Ethnicity
Hispanic 57 (4.9%) 29 (11.8%) 6 (1.5%) 57 (11.1%) 149 (6.4%)
Non-hispnaic 1100 (94.2%) 201 (82.0%) 387 (98.2%) 453 (88.5%) 2141 (92.3%)
Unknown 11 (0.9%) 15 (6.1%) 1 (0.3%) 2 (0.4%) 29 (1.3%)
Diagnosis age (years)
Mean (SD) 12.8 (3.46) 12.9 (3.66) 13.3 (3.46) 13.2 (3.27) 13.0 (3.44)
Median [Min, Max] 13.3 [0.507, 18.7] 13.5 [0.591, 18.8] 13.5 [2.65, 19.0] 13.6 [2.80, 18.9] 13.4 [0.507, 19.0]

Infliximab drug pattern

There are only 11 exposure records with treamtment started date before diagosis were excluded.

Infliximab drug pattern by site

Vedolizumab

Simalarly, we can look at another IV drug Vedolizumab.

Vedolizumab cohort

Vedolizumab cohort summary
chop
(N=131)
colorado
(N=20)
nationwide
(N=23)
nemours
(N=42)
Overall
(N=216)
Gender
Female 52 (39.7%) 11 (55.0%) 11 (47.8%) 24 (57.1%) 98 (45.4%)
Male 79 (60.3%) 9 (45.0%) 12 (52.2%) 18 (42.9%) 118 (54.6%)
Race
Black 12 (9.2%) 2 (10.0%) 4 (17.4%) 7 (16.7%) 25 (11.6%)
Other race 24 (18.3%) 3 (15.0%) 4 (17.4%) 6 (14.3%) 37 (17.1%)
White 95 (72.5%) 15 (75.0%) 15 (65.2%) 29 (69.0%) 154 (71.3%)
Ethnicity
Hispanic 9 (6.9%) 4 (20.0%) 1 (4.3%) 6 (14.3%) 20 (9.3%)
Non-hispnaic 121 (92.4%) 16 (80.0%) 22 (95.7%) 36 (85.7%) 195 (90.3%)
Unknown 1 (0.8%) 0 (0%) 0 (0%) 0 (0%) 1 (0.5%)
Diagnosis age (years)
Mean (SD) 10.9 (4.78) 11.0 (2.67) 11.4 (4.53) 13.7 (2.58) 11.5 (4.35)
Median [Min, Max] 11.5 [1.05, 18.2] 11.4 [5.15, 15.3] 12.0 [3.23, 18.9] 14.1 [7.74, 17.2] 11.9 [1.05, 18.9]

Pattern for Vedolizumab

Oral drugs

Let's look at oral drug. First, Azathioprine, which is normally taken once per day, We consider more than 90 days from last exposure as new episode.

Azathoipine

Azathoipine cohort

Azathioprine cohort summary
chop
(N=59)
colorado
(N=112)
nationwide
(N=22)
nemours
(N=110)
Overall
(N=303)
Gender
Female 28 (47.5%) 71 (63.4%) 14 (63.6%) 62 (56.4%) 175 (57.8%)
Male 31 (52.5%) 41 (36.6%) 8 (36.4%) 48 (43.6%) 128 (42.2%)
Race
Black 7 (11.9%) 8 (7.1%) 4 (18.2%) 16 (14.5%) 35 (11.6%)
Other race 8 (13.6%) 16 (14.3%) 1 (4.5%) 12 (10.9%) 37 (12.2%)
White 44 (74.6%) 88 (78.6%) 17 (77.3%) 82 (74.5%) 231 (76.2%)
Ethnicity
Non-hispnaic 59 (100%) 93 (83.0%) 22 (100%) 101 (91.8%) 275 (90.8%)
Hispanic 0 (0%) 17 (15.2%) 0 (0%) 6 (5.5%) 23 (7.6%)
Unknown 0 (0%) 2 (1.8%) 0 (0%) 3 (2.7%) 5 (1.7%)
Diagnosis age (years)
Mean (SD) 12.4 (3.28) 12.5 (3.75) 12.9 (3.47) 12.8 (3.03) 12.7 (3.38)
Median [Min, Max] 12.6 [4.68, 17.9] 12.8 [2.86, 18.6] 12.3 [7.88, 18.6] 13.1 [5.75, 17.8] 12.8 [2.86, 18.6]

Azathoipine pattern

Azathroiprine treatment episode patients count.
site episode Patients percent
chop 1 59 100
chop 2 21 36
chop 3 7 12
chop 4 3 5
chop 5 2 3
colorado 1 112 100
colorado 2 44 39
colorado 3 21 19
colorado 4 9 8
colorado 5 2 2
colorado 6 1 1
colorado 7 1 1
colorado 8 1 1
colorado 9 1 1
colorado 10 1 1
nationwide 1 22 100
nationwide 2 5 23
nationwide 3 1 5
nationwide 4 1 5
nationwide 5 1 5
nemours 1 110 100
nemours 2 26 24
nemours 3 7 6
nemours 4 2 2

Standardized treatment duration

Using Crohon's diagnosis data to last visit date as study period, we standardize the treatment duration by percentage of days account for study period.

Methotrexate

Another drugs we are going to look at is: Methotrexate. This drug has two forms: Oral or subcutaneous (subQ). We apply same rule as Azathioprine for episode definition.

Methotrexate cohort

Meththroiprine cohort summary
chop
(N=472)
colorado
(N=155)
nationwide
(N=247)
nemours
(N=303)
Overall
(N=1177)
Gender
Female 178 (37.7%) 31 (20.0%) 31 (12.6%) 81 (26.7%) 321 (27.3%)
Male 294 (62.3%) 124 (80.0%) 216 (87.4%) 222 (73.3%) 856 (72.7%)
Race
Black 41 (8.7%) 3 (1.9%) 23 (9.3%) 36 (11.9%) 103 (8.8%)
Other race 67 (14.2%) 27 (17.4%) 14 (5.7%) 47 (15.5%) 155 (13.2%)
White 364 (77.1%) 125 (80.6%) 210 (85.0%) 220 (72.6%) 919 (78.1%)
Ethnicity
Hispanic 23 (4.9%) 15 (9.7%) 3 (1.2%) 32 (10.6%) 73 (6.2%)
Non-hispnaic 445 (94.3%) 133 (85.8%) 244 (98.8%) 270 (89.1%) 1092 (92.8%)
Unknown 4 (0.8%) 7 (4.5%) 0 (0%) 1 (0.3%) 12 (1.0%)
Diagnosis age (years)
Mean (SD) 12.6 (3.54) 12.5 (3.56) 13.3 (3.18) 12.9 (3.08) 12.8 (3.36)
Median [Min, Max] 13.1 [2.02, 18.6] 12.7 [3.70, 18.3] 13.4 [2.65, 18.5] 13.2 [2.90, 18.7] 13.2 [2.02, 18.7]

Meththroiprine pattern

Meththroiprine treatment episode patients count.
site episode Patients percent
chop 1 472 100
chop 2 172 36
chop 3 79 17
chop 4 36 8
chop 5 15 3
chop 6 6 1
chop 7 5 1
chop 8 2 0
chop 9 2 0
colorado 1 155 100
colorado 2 66 43
colorado 3 24 15
colorado 4 7 5
colorado 5 1 1
nationwide 1 247 100
nationwide 2 94 38
nationwide 3 38 15
nationwide 4 11 4
nationwide 5 2 1
nationwide 6 1 0
nemours 1 303 100
nemours 2 96 32
nemours 3 20 7
nemours 4 4 1
nemours 5 1 0

Standardized Meththroiprine pattern

Using similar standarization, we can show new treatment duration by percent of study period accordingly.

Subcutaneous(SubQ) drug

Humira (adalimumab)

Given the special usage of Humira, we can look at the gaps between doses. The recommended subcutaneous dosage of HUMIRA for adult patients with Crohn's disease (CD) is 160 mg initially on Day 1 (given in one day or split over two consecutive days), followed by 80 mg two weeks later (Day 15). Two weeks later (Day 29) begin a dosage of 40 mg every other week.

Humira cohort summary

Humira cohort summary
chop
(N=449)
colorado
(N=89)
nationwide
(N=125)
nemours
(N=412)
Overall
(N=1075)
Gender
Female 199 (44.3%) 37 (41.6%) 60 (48.0%) 194 (47.1%) 490 (45.6%)
Male 250 (55.7%) 52 (58.4%) 65 (52.0%) 218 (52.9%) 585 (54.4%)
Race
Black 32 (7.1%) 5 (5.6%) 12 (9.6%) 49 (11.9%) 98 (9.1%)
Other race 68 (15.1%) 12 (13.5%) 10 (8.0%) 76 (18.4%) 166 (15.4%)
White 349 (77.7%) 72 (80.9%) 103 (82.4%) 287 (69.7%) 811 (75.4%)
Ethnicity
Hispanic 20 (4.5%) 6 (6.7%) 1 (0.8%) 58 (14.1%) 85 (7.9%)
Non-hispnaic 427 (95.1%) 80 (89.9%) 124 (99.2%) 350 (85.0%) 981 (91.3%)
Unknown 2 (0.4%) 3 (3.4%) 0 (0%) 4 (1.0%) 9 (0.8%)
Diagnosis age (years)
Mean (SD) 13.3 (3.17) 12.6 (3.37) 13.5 (3.13) 13.4 (2.97) 13.3 (3.11)
Median [Min, Max] 13.6 [2.02, 18.6] 12.8 [2.93, 18.3] 13.6 [6.43, 18.6] 13.7 [4.18, 18.0] 13.6 [2.02, 18.6]

Humira pattern

Humira lag days by visit by sites
site visit mean median
nationwide 2 372.10870 251.5
nationwide 3 346.95455 292.5
nationwide 4 261.33333 336.0
nationwide 5 411.16667 224.5
nationwide 6 154.50000 154.5
nemours 2 111.34441 29.0
nemours 3 118.93411 73.5
nemours 4 123.66019 80.5
nemours 5 118.61783 92.0
nemours 6 139.27778 97.0
colorado 2 154.19355 35.0
colorado 3 155.65854 128.0
colorado 4 130.66667 51.0
colorado 5 170.21053 100.0
colorado 6 100.13333 62.0
chop 2 59.26185 24.0
chop 3 56.83024 28.0
chop 4 69.83286 28.0
chop 5 47.52888 28.0
chop 6 53.53035 28.0

Humira treatment timeline

To check Humira treatment timeline, we also put treatment start and end in segments.

Stelara(Ustekinumab)

We assume that Stelera pattern is similar both in induction and subQ.

Stelera cohort summary

Stelera cohort summary
chop
(N=129)
colorado
(N=17)
nationwide
(N=23)
nemours
(N=66)
Overall
(N=235)
Gender
Female 66 (51.2%) 9 (52.9%) 15 (65.2%) 37 (56.1%) 127 (54.0%)
Male 63 (48.8%) 8 (47.1%) 8 (34.8%) 29 (43.9%) 108 (46.0%)
Race
Black 11 (8.5%) 3 (17.6%) 0 (0%) 7 (10.6%) 21 (8.9%)
Other race 17 (13.2%) 1 (5.9%) 1 (4.3%) 10 (15.2%) 29 (12.3%)
White 101 (78.3%) 13 (76.5%) 22 (95.7%) 49 (74.2%) 185 (78.7%)
Ethnicity
Hispanic 8 (6.2%) 1 (5.9%) 0 (0%) 12 (18.2%) 21 (8.9%)
Non-hispnaic 121 (93.8%) 16 (94.1%) 23 (100%) 54 (81.8%) 214 (91.1%)
Diagnosis age (years)
Mean (SD) 13.0 (3.07) 12.9 (2.75) 12.4 (2.90) 12.9 (3.01) 12.9 (3.00)
Median [Min, Max] 13.1 [4.02, 19.0] 12.4 [6.28, 17.7] 12.0 [6.44, 18.1] 12.5 [6.03, 18.0] 12.6 [4.02, 19.0]

Stelera Pattern

Stelera lag days by visit by sites
site visit Mean Median Q1 Q3
chop 2 49 18 6 42
chop 3 45 36 14 56
chop 4 51 40 18 56
chop 5 63 50 29 64
chop 6 56 36 26 60
chop 7 57 47 24 66
chop 8 48 30 22 53
chop 9 52 29 22 48
chop 10 52 36 27 61
chop 11 48 34 26 51
chop 12 49 29 25 54
chop 13 43 32 26 57
chop 14 49 30 26 48
chop 15 33 32 25 42
chop 16 32 30 26 40
chop 17 41 31 26 42
chop 18 131 45 40 148
chop 19 55 30 13 85
chop 20 55 28 22 42
chop 21 63 29 28 66
chop 22 22 22 21 25
chop 23 21 24 18 24
chop 24 30 30 25 36
chop 25 28 26 24 26
chop 26 30 28 28 30
chop 27 19 23 7 29
chop 28 32 29 28 32
chop 29 35 33 30 38
chop 30 22 22 13 32
chop 31 29 29 29 29
chop 32 45 45 45 45
chop 33 21 21 21 21
chop 34 40 40 40 40
chop 35 1 1 1 1
chop 36 26 26 26 26
chop 37 32 32 32 32
chop 38 60 60 60 60
chop 39 52 52 52 52
chop 40 54 54 54 54
chop 41 12 12 12 12
colorado 2 75 16 15 85
colorado 3 298 274 242 427
colorado 4 20 7 4 28
colorado 5 70 70 36 104
colorado 6 56 56 56 56
colorado 7 195 195 195 195
colorado 8 35 35 35 35
nationwide 2 439 462 56 693
nemours 2 78 21 6 55
nemours 3 105 56 20 192
nemours 4 131 103 24 208
nemours 5 167 73 32 262
nemours 6 151 120 30 182
nemours 7 94 89 14 138
nemours 8 168 130 80 208
nemours 9 20 7 4 30
nemours 10 118 118 94 143
nemours 11 109 136 89 142
nemours 12 84 67 55 104
nemours 13 56 56 56 56
nemours 14 112 112 112 112
nemours 15 56 56 56 56
nemours 16 63 63 63 63
nemours 17 56 56 56 56
nemours 18 56 56 56 56
nemours 19 1 1 1 1
nemours 20 230 230 230 230
nemours 21 152 152 152 152
nemours 22 252 252 252 252

Stelera treatment segment

Similarly, we would like to look at the timeline of Stelera treatment.